Value of plasma NCAM/ABCA1 double-labeled exosomal Aβ42 and microRNA-388-5p in early diagnosis of Alzheimer's disease
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摘要:
目的 检测神经细胞黏附分子(NCAM)和三磷酸腺苷(ATP)结合盒转运体A1(ABCA1)双标记外泌体内Aβ42和microRNA-388-5p(miR-388-5p),并分析其在阿尔茨海默病(AD)早期诊断中的潜在价值。 方法 检测67例主观认知下降(SCD)、65例遗忘型轻度认知障碍(aMCI)、68例痴呆期阿尔茨海默病(DAT)患者、60例健康对照组受试者及60例血管性痴呆(VaD)的疾病对照组患者的血浆NCAM/ABCA1外泌体Aβ42和miR-388-5p水平,分析各指标间的相关性及其对疾病发展阶段的诊断效能。 结果 SCD、aMCI和DAT受试者血浆NCAM/ABCA1双标外泌体Aβ42水平均显著高于VaD和健康对照组受试者(P<0.05);SCD、aMCI和DAT受试者血浆NCAM/ABCA1双标外泌体miR-388-5p含量均显著低于VaD及对照组受试者(P<0.05)。 血浆NCAM/ABCA1双标外泌体内Aβ42对SCD、aMCI和DAT诊断的敏感度和特异度均高于miR-388-5p。 结论 本研究提示NCAM/ABCA1双标外泌体中Aβ42和miR-388-5p可作为aMCI和SCD诊断或预警的候选标志物,但尚需纵向多中心研究以进一步证实。 Abstract:Objective To detect the dual-labeled Aβ42 and miR-388-5p in exosomes of nerve cell adhesion molecule (NCAM) and ATP binding cassette transporter A1 (ABCA1), and analyze their potential value in the early diagnosis of Alzheimer's disease (AD). Methods The levels of plasma NCAM/ABCA1 exosomes Aβ42 and miR-388-5p of 67 cases of subjective cognitive decline (SCD), 65 cases of amnestic mild cognitive impairment (aMCI), 68 Alzheimer's disease cases with dementia (DAT), 60 healthy controls and 60 controls of vascular dementia (VaD) cases were detected, and the correlation between the indicators and the diagnostic power of each disease stage were analyzed. Results The plasma levels of NCAM/ABCA1 double-labeled exosomes Aβ42 in SCD, aMCI and DAT cases were significantly higher than those in controls of VaD cases and healthy controls (P<0.05). In plasma NCAM/ABCA1 of SCD, aMCI and DAT cases, the content of miR-388-5p in double-labeled exosomes was significantly lower than those of controls of VaD cases and healthy controls (P<0.05). The sensitivity and specificity of plasma NCAM/ABCA1 double-labeled exosomal Aβ42 for SCD, aMCI and DAT were higher than those of miR-388-5p. Conclusion This study suggests that Aβ42 and miR-388-5p in NCAM/ABCA1 double-labeled exosomes can be used as candidate markers for the diagnosis or early warning of aMCI and SCD, but longitudinal multicenter studies are still needed to further confirm the results. -
Key words:
- Alzheimer's disease /
- Diagnosis /
- Exosome /
- Amyloid β /
- MicroRNA
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表 1 不同受试组总Aβ42和双标外泌体内Aβ42的吸光度
Table 1. Total Aβ42 and Aβ42 absorbance in double-labeled exosomes in different groups
分组 总Aβ42 双标外泌体内Aβ42 P值 与DAT比较 与aMCI比较 与SCD比较 与VaD比较 对照组 3.12±0.59 1.03±0.28 0.003/<0.001 0.028/<0.001 0.092/0.019 0.139/0.088 VaD 3.09±0.61 1.08±0.31 0.007/<0.001 0.039/<0.001 0.188/0.065 1.000/1.000 SCD 2.93±0.56 1.36±0.33 0.013/<0.001 0.072/0.008 1.000/1.000 0.188/0.065 aMCI 2.81±0.43 2.01±0.35 0.009/<0.001 1.000/1.000 0.072/0.008 0.039/<0.001 DAT 2.56±0.38 3.09±0.43 1.000/1.000 0.009/<0.001 0.013/<0.001 0.007/<0.001 注:P值分别表示为总Aβ42/双标外泌体内Aβ42与不同受试组的两两比较。VaD. 血管性痴呆;SCD. 主观认知下降;aMCI. 遗忘型轻度认知障碍;DAT. 痴呆期阿尔茨海默病;P值栏数据表示为“总Aβ42组间比较的P值/双标外泌体内Aβ42组间比较的P值” 表 2 不同受试组总MiR-388-5p和双标外泌体内MiR-388-5p的水平
Table 2. Total MiR-388-5p and double-labeled exosome MiR-388-5p levels in different groups
分组 总miR-388-5p 双标外泌体内miR-388-5p P值 与DAT比较 与aMCI比较 与SCD比较 与VaD比较 对照组 1.51±0.35 2.93±0.49 0.002/<0.001 0.033/<0.001 0.102/0.025 0.156/0.093 VaD 1.55±0.43 0.82±0.43 0.013/<0.001 0.049/<0.001 0.233/0.036 1.000/1.000 SCD 1.35±0.29 2.38±0.35 0.025/<0.001 0.093/0.001 1.000/1.000 0.233/0.036 aMCI 1.22±0.23 1.33±0.20 0.002/<0.001 1.000/1.000 0.093/0.001 0.033/<0.001 DAT 0.77±0.11 0.81±0.13 1.000/1.000 0.002/<0.001 0.025/<0.001 0.013/<0.001 注:P值分别表示总miR-388-5p /双标外泌体内miR-388-5p与不同受试组的两两比较。VaD.血管性痴呆;SCD. 主观认知下降;aMCI. 遗忘型轻度认知障碍;DAT. 痴呆期阿尔茨海默病;P值栏数据表示为“总miR-388-5p组间比较的P值/双标外泌体内miR-388-5p组间比较的P值” 表 3 各组内Aβ42与miR-388-5p相关性分析
Table 3. Correlation analysis between Aβ42 and miR-388-5p in each group
Aβ42与
miR-388-5p来源对照组 VaD SCD aMCI DAT 总体分析 r值 P值 r值 P值 r值 P值 r值 P值 r值 P值 r值 P值 血浆总量 0.491 0.003 0.438 0.017 0.382 0.035 0.417 0.011 0.450 0.009 0.423 0.021 血浆双标外泌体 −0.634 <0.001 −0.672 <0.001 −0.528 <0.001 −0.692 <0.001 −0.685 <0.001 −0.653 <0.001 注:P值表示为相关性分析的统计结果。VaD. 血管性痴呆;SCD. 主观认知下降;aMCI. 遗忘型轻度认知障碍;DAT. 痴呆期阿尔茨海默病 表 4 受试者工作特征曲线和诊断效能分析结果
Table 4. Receiver operating characteristic curve and diagnostic performance analysis results
分组 来源 项目 曲线下
面积标准误 95%置信区间 截断值 P值 敏感度(%) χ2值 特异度(%) χ2值 下限 上限 SCD 血浆总体 Aβ42 0.525 0.019 0.506 0.544 1.29 0.002 62.5 38.969 66.3 37.592 miR-388-5p 0.529 0.029 0.500 0.558 2.93 0.001 61.5 63.3 外泌体内 Aβ42 0.683 0.029 0.654 0.712 1.02 0.006 73.5a 48.956 71.4 a 51.015 miR-388-5p 0.615 0.020 0.595 0.635 2.77 <0.001 67.3 66.3 aMCI 血浆总体 Aβ42 0.677 0.021 0.656 0.698 1.98 0.005 68.6 36.957 68.3 37.569 miR-388-5p 0.621 0.020 0.601 0.641 1.85 0.017 67.2 67.5 外泌体内 Aβ42 0.739 0.031 0.701 0.770 1.77 0.003 72.3 39.871 71.9 36.755 miR-388-5p 0.662 0.023 0.639 0.685 1.65 <0.001 69.5 70.3 DAT 血浆总体 Aβ42 0.771 0.030 0.741 0.801 3.01 0.003 70.2 38.215 70.1 37.567 miR-388-5p 0.709 0.028 0.681 0.737 1.23 0.002 68.8 69.5 外泌体内 Aβ42 0.815 0.035 0.780 0.850 2.69 <0.001 79.3 a 45.639 81.3 a 47.051 miR-388-5p 0.769 0.028 0.701 0.757 0.97 <0.001 73.1 75.7 注:a. 与同组的miR-388-5p相比P<0.05。SCD. 主观认知下降;aMCI. 遗忘型轻度认知障碍;DAT. 痴呆期阿尔茨海默病 -
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